The effects of genetic alterations of retroviruses include the generation of variant viruses which infect different hosts; viruses which are capable of infecting different tissues in the host; and virus variants which exhibit enhanced pathogenicity compared to the "wild type" virus. Such alterations have been documented with nearly all groups of retroviruses, including avian, murine, equine, and most recently with HIV, the etiological agent of AIDS. This project is largely focused on the genetic alteration of murine leukemia viruses (MuLVs), principally with regard to alterations due to recombination and the role of this process in disease induction. Previous studies include the identification of a novel recombinant virus which provided a detailed model for the generation of oncogenic viruses in mice which exhibit a high incidence of leukemia. In our current studies we have demonstrated the generation of a variant virus in cell culture by spontaneous recombination between viruses postulated as intermediates in our model. The variant virus exhibits in vitro properties indistinguishable from those of oncogenic recombinant viruses isolated from mice, and is currently being tested for in vivo oncogenicity. Other studies have demonstrated that the viral envelope protein strongly influences the tissue in which viruses replicate at early times alter inoculation, whereas viral sequences which control the rate of transcription influence tissue-specific expression at later times. These results have been extended to show that early pathological events in leukemia induction are influenced by the viral envelope protein, while the type of leukemia which subsequently develops at later times is influenced by transcriptional control elements. Many of these studies have been greatly facilitated by the development of a retrovirus assay on live cells using monoclonal antibodies. To further extend the usefulness of this assay we have developed a broadly reactive monoclonal antibody directed at the envelope proteins of MuLVs. The antibody facilitates the assay of a very broad spectrum of MuLVs, including the amphotropic MuLVs for which no monoclonal antibodies directed at the envelope protein have been described.